Safeguarding American Agriculture 

Federal Relay Service 

APHIS is an agency of USDA’s Marketing and Regulatory Programs (Voice/TTY/ASCII/Spanish)

An Equal Opportunity Provider and Employer 1-800-877-8339 

May 2, 2012 

CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 12-09 

TO: Biologics Licensees, Permittees, and Applicants 

 Directors, Center for Veterinary Biologics 

 Veterinary Services Leadership Team 

 

FROM: Richard E. Hill, Jr. /s/ Richard E. Hill, Jr. 

 Director 

 Center for Veterinary Biologics 

SUBJECT: Licensing of Vaccines as Preharvest Food Safety Interventions 

I. PURPOSE 

The purpose of this Notice is to provide additional guidance regarding the licensing 

process for products designed primarily for use as Preharvest Food Safety Interventions. 

II. BACKGROUND 

The licensing of veterinary biological products, further described here as a vaccine, 

involves a series of steps that satisfactorily demonstrates the purity, safety, potency, and 

efficacy of the intervention. In simplest terms, this involves the following: 

 A demonstration of the purity and identity of the seed and cell line used in 

producing the immunogen 

 Demonstration of a consistent vaccine production process 

 Demonstration of efficacy, where efficacy generally reflects the prevention or 

mitigation of clinical disease in the host animal 

 Demonstration of safety in the host animal in a full-scale field trial setting 

 Validation of a potency assay that measures the potency of serials of vaccine 

 Successful production of commercial scale serials of vaccine (Prelicensing 

Serials) 

The licensing of Preharvest Food Safety (PHFS) vaccines follows this same basic 

framework except the vaccines are targeted at the reduction or elimination of the carrier 

state of organisms (Center for Veterinary Biologics Notice No. 05-07). This Notice 

indicates that products will be required to show significant, meaningful, and relevant 

efficacy. Additionally, the Notice indicates that for claims of reduction of colonization 

and/or shedding, products must demonstrate the ability to cause a substantial decrease in 

the number of animals colonized and/or numbers of organisms shed by vaccinated 

animals. To date, a very limited number of studies have been designed and conducted to 

United States 

Department of 

Agriculture 

Animal and Plant 

Health Inspection 

Service 

Veterinary Services 

Center for Veterinary 

Biologics 

1920 Dayton Avenue 

PO Box 844 

Ames, IA 50010 

(515) 337- 6100 
CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 12-09 

Page 2 

explicitly address these criteria. Licensing PHFS products can present some unique 

challenges due to the limited understanding of the factors affecting prevalence in the field 

setting (e.g., E. coli O157:H7) and the limitations associated with experimental 

vaccination-challenge studies. The Center for Veterinary Biologics (CVB) experience 

has been that industry has moved forward with studies without adequate consideration of 

study designs reflective of these factors and adequate dialogue with licensing staff prior 

to initiating said studies. 

In addition, the Center has encountered an unexpected resurgence in firm interest in 

citing data from peer-reviewed articles to support the efficacy of their vaccine candidates. 

While the CVB recognizes the important contribution that independent research can 

provide in the conceptualization and discovery stages of product development, data from 

peer-reviewed articles are not considered to be adequate for the sole purpose of product 

licensing or establishing label claims related to product performance. This long standing 

guidance is described in detail in Veterinary Services Memorandum 800.98. 

As a step to make available vaccines to meet an emergency condition, limited market, 

local situation, or other special circumstances, the Animal and Plant Health Inspection 

Service (APHIS) can issue a Conditional License for products that have demonstrated 

safety and purity and for which a “reasonable expectation of efficacy exists”. Due to the 

critical nature of ensuring that biological products are not dangerous or harmful, the 

safety and purity standards for conditionally licensed products do not vary from those 

expected from fully licensed products. However, the criterion for demonstrating a 

reasonable expectation of efficacy varies based on the unique circumstances associated 

with each emergent disease situation. For PHFS vaccines considered to date, CVB has 

applied the expectation that the product will consistently result in some degree of positive 

vaccine effect. 

III. POLICY 

For all the reasons mentioned previously, and based on data from some of the early 

exploratory-type efficacy studies, it appears that large scale field efficacy studies will 

provide the best opportunity for applicants to successfully demonstrate the utility of their 

vaccine intervention in an environment reflective of the intended product usage. Due to 

the inherent complexities associated with designing these types of studies, firms are 

encouraged to begin a dialogue with their respective licensing staff as early as possible in 

the licensing process, and to take advantage of some new program initiatives and process 

improvements recently undertaken by CVB. 

To provide additional assistance to industry, the CVB has undertaken an initiative to 

create comprehensive product licensing plans for each new product proposed for 

licensure or permit for distribution and sale. Ideally, the development of these plans will 

be a cooperative effort between the applicant and CVB. 

In addition to the core product licensing plan, the applicant has the opportunity to discuss 

specific approaches to fulfill each of the licensing requirements within the product 
CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 12-09 

Page 3 

licensing plan and may enter into Critical Path Agreements with APHIS, as desired. As 

defined in Center for Veterinary Biologics Notice No. 11-12, a Critical Path Agreement 

provides formal documentation of an agreement in principle regarding the study design 

or approach needed to fulfill a regulatory requirement. 

The CVB recognizes that unique and significant challenges associated with designing and 

conducting studies to demonstrate efficacy for PHFS products can exist. CVB continues 

to actively engage firms in designing studies that provide the ability to demonstrate 

significant, meaningful and relevant reductions in prevalence and/or shedding in support 

of product efficacy. While not all applicants may choose to enter into a Critical Path 

Agreement, the CVB continues to encourage all applicants to work closely with them in 

the development of PHFS efficacy study protocols in order to maximize the efficiency of 

the licensing process. 

Applicants are reminded that label claims and advertising must contain only factual 

statements supported by data (e.g., as an aid in the reduction of colonization and/or 

shedding). No food safety or human health claims, either implicit or explicit, would be 

allowed by APHIS. Products with such claims would fall under the authority of the FDA 

and require their approval.